Downregulating hypoxia-inducible factor-1α expression with perfluorooctyl-bromide nanoparticles reduces early brain injury following experimental subarachnoid hemorrhage in rats

作者：Xu, Wei; Xu, Rui; Li, Xia; Zhang, Huan; Wang, Xin^*; Zhu, Ji^*

来源：American Journal of Translational Research, 2016, 8(5): 2114-2126.

• Early brain injury
• hypoxia-inducible factor 1 alpha
• perfluorooctyl-bromide
• subarachnoid hemorrhage
• vascular endothelial growth factor

The aim of the present study was to investigate the effects of perfluorooctyl-bromide (PFOB) nanoparticles on hypoxia-inducible factor 1 alpha (HIF-1 alpha) and its downstream target genes in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Healthy male Sprague Dawley rats (n=100) were randomly divided into five groups: Sham, SAH, SAH + vehicle, SAH + 5 mg/kg PFOB and SAH + 10 mg/kg PFOB. A rat model of SAH was created by endovascular perforation, and PFOB treatment (5 mg/kg or 10 mg/kg injected into the caudal vein) was initiated 1 h after SAH. All rats were subsequently sacrificed 24 h after surgery. Treatment with PFOB significantly alleviated EBI (including neurological dysfunction, brain edema, blood-brain barrier disruption (BBB), and neural cell apoptosis). In addition, it also suppressed the expression of HIF-1 alpha, vascular endothelial growth factor (VEGF) and BNIP3 in the rat hippocampus. The effects of 10 g/kg PFOB were found to be more obvious than those of 5 g/kg PFOB. Our work demonstrated that PFOB treatment alleviated EBI after SAH, potentially through downregulation of the expression of HIF-1a and its target genes, which led to reduced cell apoptosis, BBB disruption and brain edema.

• 出版日期2016
• 单位重庆医科大学